Blackwood et al, in U.S. Pat. No. 2,984,686, assigned to Chas. Pfizer & Co., Inc. and issued May 16, 1961, disclose the production of 6-methylene-5-oxytetracycline and its 7-halo derivatives; the same procedure is shown for other tetracyclines by Blackwood et al, with one further collaborator, in the Journal of the American Chemical Society, Vol. 85 (1965) at pages 3943 to 3953. All of the products have antibiotic properties of varying degree, generally being at least as strong as the starting product; 6-methylene-5-oxytetracycline is particularly useful, possessing better properties than the initial reactant, oxytetracycline.
Blackwood et al's basic process involves (1) 11ahalogenation of a tetracycline, either in base or salt form, to produce an 11a-halo-6,12-hemiketal; (2) dehydration of the hemiketal to the 11a-halo-6-methylene derivative; and (3) reduction of this halo-methylene derivative, in the salt form, to the end product. The process as described is characterized by low over-all yields, resulting in high costs.